Tissue transglutaminase: an enzyme with a split personality

Tissue transglutaminase (tTG) belongs to the family of transglutaminase enz ymes that catalyze the posttranslational modification of proteins via Ca2+- dependent cross-linking reactions. The catalytic action of tTG results in t he formation of an isopeptide bond that is of great physiological significa nce since it is highly resistant to proteolysis and denaturants. Although t TG-mediated cross-linking reactions have been implicated to play a role in diverse biological processes, the precise physiological function of the enz yme remains unclear. Recent data, however, suggest that the protein polymer s resulting from tTG-catalyzed reactions may pray a role in commitment of c ells to undergo apoptosis. On the same token, tTG-mediated formation of ins oluble protein aggregates may underlie the markers of numerous pathological conditions, such as the senile plaques in Alzheimer's disease and the Lewy bodies in Parkinson's disease. In addition to catalyzing Ca2+-dependent cr oss-linking reactions, tTG can also bind and hydrolyze guanosine triphospha te and adenosine triphosphate. By virtue of this ability, tTG has been iden tified as a novel G-protein that interacts and activates phospholipase C fo llowing stimulation of the alpha-adrenergic receptor. The ability of tTG to mediate signal transduction may contribute to its involvement in the regul ation of cell cycle progression. The following review summarizes the import ant features of this multifunctional enzyme that have emerged as a result o f recent work from different laboratories. (C) 1999 Elsevier Science Ltd. A ll rights reserved.